Translational Evaluation of a Disodium Adenosine Monophosphate (AMP2Na)-Based Topical Formulation for Physiology-Aligned Skin Rejuvenation: Integrated In Vitro, Ex Vivo, and Clinical Evidence

Abstract

Skin aging stems from intrinsic decline and external stressors that induce oxidative stress and mitochondrial damage, ultimately lowering cellular energy production and slowing epidermal turnover to cause wrinkles, dryness, and pigment imbalances. While disodium adenosine monophosphate (AMP2Na) is hypothesized to enhance cellular adenosine triphosphate production and restore epidermal metabolism, its broader anti-aging effects have remained underexplored. To address this, a multi-tiered study integrating in vitro, ex vivo, and clinical investigations was conducted. Specifically, a 12-week exploratory clinical trial involving female participants with facial hyperpigmentation (n = 23), alongside a short-term forearm study (n = 22), suggested that the AMP2Na-containing product could reduce wrinkles and hyperpigmentation while safely improving hydration, barrier function, skin lifting, and epidermal turnover with high participant satisfaction. Mechanistically, in vitro assays on human dermal fibroblasts showed that the formulation restored antioxidant enzyme activity and mitigated senescence. Ex vivo UVB-irradiated skin explant models corroborated these findings by revealing reduced melanin levels, preserved collagen and elastin networks, and an upregulation of key structural and barrier-related proteins. Ultimately, by potentially supporting epidermal turnover and restoring barrier function through this biomimetic mechanism, the AMP2Na-containing product might offer a promising option for alleviating wrinkles, dryness, and hyperpigmentation. Future randomized, vehicle-controlled clinical trials and comprehensive laboratory studies are warranted to validate its true potential in skin rejuvenation.